A profile of HIV patients in YMCH with special referance to

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A PROFILE OF HUMAN IMMUNODEFFICIENCY VIRUS
INFECTED PATIENTS IN YENEPOYA MEDICAL COLLEGE
HOSPITAL WITH SPECIAL REFERANCE TO CORRELATION
BETWEEN CD4 COUNT AND TOTAL LYMPHOCYTE COUNT
1. INTRODUCTION
The world wide epidemic of Human Immuno deficiency Virus (HIV) is an
international health problem of extraordinary scope and unprecedented urgency1.
Since 1980 till today HIV epidemic has continued its dramatic expansion universally,
both geographically and in terms of risk groups. The epidemiological scenario is also
changing, from a disease mainly of
homosexual males to a rapidly growing
population of HIV infected females, children and men who are not homosexuals. The
spectrum of HIV infection includes asymptomatic cases to AIDS at other extreme.
The diagnosis rests on clinical manifestations and laboratory markers.
In India, the socioeconomic and cultural environment is important in
disease transmission and prevalence, as also the clinical spectrum is very different
from western society. One of the purposes of this study is to know the different
patterns of clinical presentation of HIV infection in this region
Soon after HIV was found to be the cause of AIDS, it was shown that the
virus binds to receptors on CD4 cells, enters the cells, and uses them to create new
virus, destroying them in the process. This results in the depletion of CD4 cells and
immunodeficiency.2
With the increased availability of equipment to perform CD4 counts and the
knowledge that CD4 cells were the primary target of HIV, the determination of CD4
count became the standard measure of immunodeficiency in adult HIV-infected
patients in resource-rich countries. The relative ease of CD4 cell monitoring also led
to its advocacy in treatment guidelines for determining when to start, stop, or change
ART and for deciding when to initiate prophylaxis for opportunistic infections (OIs).
This is despite the fact that CD4 count does not always correlate with functional
immunity; some patients with normal CD4 counts are susceptible to OIs and some
patients with significantly depressed CD4 counts do not seem unduly susceptible to
OIs.
The determination of CD4 cell count and percentage is too expensive for
most health facilities in resource-poor countries to perform routinely3. In contrast,
TLC can be derived easily in resource-poor countries by performing a routine white
blood cell count.
TLC is the total white blood cell count multiplied by the
lymphocyte percentage; for example, a total white blood cell count of 6,000 cells / µL
with a lymphocyte percentage of 30% would result in a TLC of 1,800 cells / µL3. The
equipment and skills to perform total white blood cell count and differential are
readily available in most hospitals and clinics in resource-poor countries. The need to
rapidly expand the use of ART in resource-poor countries as well as the human
resource constraints, cost, and infrastructure concerns surrounding CD4 cell
measurements have prompted to evaluate the utility and predictability of TLC as a
measure of immune function and its usefulness in guiding initiation of ART. This
study also attempts to correlate CD4 count with TLC
4. MATERIALS AND METHODS
Design: Prospective study of 2yrs from October 2005 to October 2007.
Setting: Yenepoya Medical college Hospital
1.Inclusion Criteria
Adult HIV positive patients above 16yrs with a definite diagnosis of HIV
Illness by CDC revised surveillance.
2. Exclusion Criteria
1. Pediatric HIV positive patients.
2. Patients on immunosuppressant therapy.
3. Patients who are diagnosed as HIV positive earlier and on treatment for the
same.
Patient Enrollment and Monitoring
50 cases of HIV positive patients were recruited from all treating units at
Yenepoya Medical College Hospital from October 2005 to October 2007.
These pts were also treated for opportunistic infections.
Method of collection of Data
Diagnosis of HIV was made in these patients by
Detailed clinical history and physical examination.
Routine laboratory investigations including Elisa (2 ELISA).
Venous samples were sent for evaluation of CD4 count (by Flow cytometric
method). At the same time samples were sent for evaluation of TLC.
Total lymphocyte count (TLC) was calculated by multiplying the differential
lymphocyte count with the total leucocyte count. [TLC=Total leucocyte count x
Differential lymphocyte count]
In the patients who were symptomatic, the following investigations were done.
Collection and processing of specimens.
Various samples e.g. sputum, oral swab, blood, stool, urine, cerebrospinal
fluid (CSF), lymph node aspirate were collected as per symptoms and clinical
presentations. All the specimens were collected under universal aseptic precautions in
suitable sterile containers.
Oral swab
Oral swabs were collected in cases presenting with oral thrush. Two sterile
swabs were taken and each rubbed against the right tonsil and rolled along the soft
palate to the left tonsil. Curdy white patches were also swabbed. Gram staining
was done with one swab and the other swab was streaked on sabourauds dextrose agar
slope. Germ tube test was also performed for presumptive identification of candida
Albicans
Stool
Fresh samples of stool were collected in sterile, dry, leak proof, wide-mouth
container.
Wet mount- Direct saline mounts and iodine mounts were screened under
microscope for helminthes eggs, larvae, protozoan cysts, trophozoites, pus cells and
possible fungal elements. After concentration method supernatants were discarded,
sediment was used for Kinyoun cold test for detection of oocysts of cryptosporidium,
cyclospora, isospora and sarcocystis.
Sputum
Early morning sputum was collected in a wide mouthed sterile container.
Instructions were given to rinse the mouth with tap water before sample collection,
and to collect expectoration and not saliva.
Wet mount- sputum sample was taken on a clean glass slide and 2 drops of
10% KOH was added and covered with a cover slip. Slip was kept in incubator at
37degree c for 1O mins and examined for fungal elements.
Staining of sputum was done for detection of
 Gram stain- to see pyogenic bacteria, pus cells and epithelial cells

Ziehl- Neelsen stain for acid fast bacilli

Methanamine silver nitrate stain- for the detection of pneumocystis carini
cysts
Urine
Mid stream urine samples were collected in sterile container. All the samples
were processed within one hour of collection . Gram stain- done to detect pus cells,
epithelial cells, bacteria and yeast cells.
Cerebrospinal fluid (CSF)
CSF samples were obtained by lumbar puncture and processed immediately.
CSF fluid was sent to microbiology for
 Culture
 Staining- gram stain, Ziehl-Neelsen's stain and methylene blue stains were
used to detect different pathogens
 India ink wet mount- it was done to detect presence of Cryptococus.
Blood
Skin at the site of venepuncture was cleaned with 70% alcohol followed by
2% tincture iodine. Total 15ml blood was collected from each patient. 10ml was used
for blood culture and 5m1 was collected in sterile pencillin vial for serological tests.
Serology
The blood collected in pencillin vial was allowed to clot. Samples were
centrifuged and serum was collected for following tests

VDRL

HbsAg

HCV
Method of Statistical Analysis
Sensitivity and specificity of various total lymphocyte count cut off were
computed for CD4 count <200 cells/mm3. Correlated and statistical indices computed
for all pts
Sensitivity, Specificity, Positive Predictive value and Negative Predictive value:
TLC values at 1200 or < compared with CD4 values at <200, then the number
of patients with True Positive (TP), False Positive (FP), True Negative (TN) and False
Negative (FN) determined. The following were calculated :
Sensitivity : [TP/(TP+FN)]
Specificity : [TN/ (TN+FN)]
Positive Predictive Value : PPV = [TP/(TP+FN)]
Negative Predictive Value : NPV =[TN/(FN+TN)
In the above test P value less than 0.05 were taken to be statistically significant.
The data was analysed using Stastical Package for Social Science (SPSS) package.
4. RESULTS AND ANALYSIS
A total number of 50 cases of HIV infected patients admitted in Yenepoya
Medical College Hospital, Mangalore who met the inclusion criteria were studied.
1. AGE AND SEX DISTRIBUTION :
Table No. 1 : The age and sex distribution.
Age i n years
Mal e
Fe mal e
T otal
<20
_
_
_
21 -30
12
1
13
31 -40
20
2
22
41 -50
10
2
12
51 -60
2
_
2
>61
1
_
1
Out of the 50 cases studied, 45 (90%) were males and the remainder 5 (10%)
were females. Their ages ranged from 20 years to 60 years with a mean of 38.08 ±
9.01. The ratio of
Male : Female was 9 : 1. The maximum incidence of 70% was
seen in the age group between 20 to 40 years, of which 91.42% (32/35) were males.
FIGURE No : 1
AG E AND S E X D IS T R IB UT ION
male
female
25
Num ber in years
20
15
20
10
12
5
0
10
0
1
2
2
< 20
21-30
31-40
41-50
2
0
1
0
0
Ag e in ye a rs
51-60
> 60
2. OCCUPATION:
Table No. 2: Sex Wise Distribution Of Different Types Of Occupations :
Male
Female
Total
Transport
17
-
17
Farmers
5
-
5
Hotel workers
11
-
-
Labourers
7
1
8
Others
5
4
9
Out of the 50 cases studied, 34% (17/50) were in transport, 22% (11/50) were
hotel workers, 16% (8/50) were labourers, and the rest constituted farmers,
businessmen, housewives.
FIGURE : 2
Distribution of types of occupation
17
11
11
8
Others
Labourers
Hotel work
Agriculture
Transport
5
3. MODE OF TRANSMISSION :
Out of 50 cases, 64% (32/50) had heterosexual (multiple sexual partners),
Homosexual 10% (5/50), Blood transfusion 0.5% (1/50) and mode of transmission
and history could not be obtained in 24% (12/50).
FIGURE : 3
DURATION SINCE TIME OF FIRST RISK EXPOSURE:
Duration since time of first risk exposure ranged from 2 years to 20 years with
the mean of 8.27 ± 4.181.
5. PRESENTING SYMPTOMS
Table No. 3: Sex wise distribution of presenting symptoms :
Presenting symptoms
Male
Female
Total
Fever > 1 month
36
4
40
Cough
27
2
29
Diarrhoea >Imonth
9
2
11
Significant weight loss
39
3
42
Abdominal pain
10
-
10
Headache
5
1
6
Seizures
3
-
3
Altered sensorium
2
0
2
Dysphagia
1
1
2
Ear discharge.
1
-
1
Out of 50 cases, most common presenting symptoms were fever of more
than 1 month in 80% (40/50) and significant weight loss in 84% (42/50), 58% (29/50)
had cough out of which 40% (20/50) had expectoration. 22% (11/50) had diarrhoea of
more than 1 month. Pain abdomen was complained by 20% (10/50) of patients, 12%
(6/50) had headache and 6% (3/50) had seizures of generalized tonic clonic type.
Two patients presented with altered sensorium and two with dysphagia. Purulent
discharge from the ear was complained by one patient.
3
2
2
1
altered sensorium
Dysphagia
Ear d/d
6
seizures
head ache
11
Abdominal pain
40
significant wt loss
Diarhoea>1m
cough
fever >1m
Number of patients
FIGURE:4
Distribution of presenting symptoms
42
29
10
6. CLINICAL SIGNS :
Table No. 4: Sex wise distribution of clinical signs :
Signs
Male
Female
Total
Lymphadenopathy
17
3
20
Oral candidiasis
10
3
13
Skin lesions
7
0
7
Of the total number of patients studied on general physical examination, 40% (20/50)
had palpable lymphnodes, 26% (13/50) had oral candidiasis, 14% (7/50) had skin
manifestations and commonest manifestation was papular eruption seen in 42.85%
(3/7) of cases, seborrheic dermatitis, hypopigmented macules, penile ulcer were seen
in 57.16% (4/7) cases.
FIGURE : 5
Number of patients
DISTRIBUTION OF CLINICAL SIGNS
20
13
7
Lymphade nopathy Oralcandidiasis
7. LABORATORY PROFILE:
Skin le sions
Haemoglobin
estimation was done in 50 cases. 14% (7/50) had a
haemoglobin of less than 8gm% and 26% (13/50) had haemoglobin of more than
12gm% with mean of 10.42 ± 1.99. Peripheral smear in 62% of cases were
normocytic normochromic type.
Table No. 5 : Sex wise Distribution of Haemoglobin Levels
Haemoglobin in gm%
Male
Female
Total
<8
8 – 10
4
16
3
1
7
17
10 – 12
12
1
13
>12
13
-
13
FIGURE : 6
Number of patients
DISTRIBUTION OF HEMOGLOBIN LEVELS
17
16
13
4
<8
8 to 10
10 to 12
>12
Gram % of hemoglobin
Table No. 6: Sex wise distribution of peripheral smear study
Peripheral smear
Male
Female
Total
Microcytic hypochromic
14
2
16
Normocytic
28
3
31
Normocytic hypochromic
0
0
0
Dimorphic
2
0
2
Thrombocytopenia
I
0
1
Normochromic
TLC vs. CD4+ COUNT
The overall mean baseline CD4+ counts in study group was 175 cells/mm3
while the overall mean baseline Total Lymphocyte count (TLC) in study group was
1338 cells/mm3.There is a fair positive correlation between CD4 count and TLC
( r = 0.55, p= <0.0001).
Table No : 7 Pearson Partial Correlation Coefficient
TLC
CD4
r:
0.55
p : <0.0001
Figure No : 7 Scatter plot of CD4+ counts vs TLC
Table No : 8 CD4+ Count < 200 vs TLC < 1200
TLC
<200
<1200
>1200
Total
No
20
13
33
%
60.61%
39.39%
No
2
15
%
11.76%
88.24%
No.
22
28
CD4
>200
Total
17
50
When patients with CD4 count of <200 cells/mm3 and TLC of <1200
cells/mm3 were correlated, the result showed a highly significant stastical correlation
(P <0.001) with sensitivity of 91% and specificity of 53% and positive prediction
value of 70% and negative prediction value of 30%
CHEST X - RAY :
Table No.9 : Sex wise distribution of various chest X-ray patterns.
Type of lesion
Upper
Male %
Female %
Total %
17.8
0
17.8
39.28
7.14
46.42
10.71
0
10.71
7.1
3.61
10.71
3.57
0
3.57
3.57
0
3.57
7.14
0
7.14
zone
lesions
B/L
infiltrations
Lower
zone
lesion
Pleural
effusion
Pneumothora
x
Cardiomegaly
Miliary
mottling
Out of 50 patients studied, 28 had radiological abnormalities. There were apical
lesions in 5, bilateral extensive infiltrations in 13, cardiomegaly in 1, pleural effusion in 3,
lower lobe opacities in 3, pneumothorax in 1 and miliary mottling in 2.
FIGURE No : 8
Distribution of chest x-ray findings
Number of patients
46.42
17.8
10.71
10.71
3.57
Cardiomegaly
Miliary motling
3.57
Pneumothrx
Pl.effusion
L.zone lesions
B/L infiltrations
Apical u.zone lesions
7.14
Chest x-ray findings
Opportunistic infections and other associated conditions
patients
in HIV infected
Tuberculosis:
Out of 50 cases studied, tuberculosis was the commonest opportunistic
infection with 68% (34/50) of cases having tuberculosis. 38.23% (13/34) had only
pulmonary tuberculosis, 38.23% (13/34) had only extra pulmonary tuberculosis and
23.53% (8/34) had both pulmonary and extra pulmonary tuberculosis.
FIGURE No: 9
Secondary Infections:
Out of 50 cases, 6% (3/50) had secondary bacterial non opportunistic
infections, out of which 2 were pneumonia caused by gram negative bacilli and 1 was
chronic suppurative otitis media.
Neurological manifestations:
Out of 50 cases, 28% (14/50) had neurological manifestations. Out of them
50% (7/14) had tubercular meningitis, 14.28% (2/14) had tuberculoma, 14.28% (2/14)
had tubercular arachnoiditis presenting with myeloradiculopathy. 1 patient was
diagnosed to have HIV encephalopathy (AIDS dementia complex) and 2 patients had
progressive multifocal leukoencephalopathy.
FIGURE No : 10
perc entag e of c as es
Dis tribution of various Neurolog ic al
s ymptoms
50
14.28
14.28
14.28
7.14
Tuberc ular
meningitis
Tuberc uloma
TB arac hnoiditis A IDS dementia
P ML
Neurologic al s ymptoms
Sexually transmitted diseases :
One patient, that is 2% (1/50) had gonorrhoea and one patient was diagnosed to
have hepatitis B.
Persistant generalized lymphadenopathy was found in one out of 50 cases studied.
Renal manifestation:
Out of 50 cases studied, one patient had HIV associated nephropathy and one
patient had chronic renal failure.
Malignancy:
Out of 50 cases studied, one patient had Non Hodgkins lymphoma and in one
patient probable diagnosis of Kaposi’s Sarcoma was made.
Fever of Unknown Origin:
Out of 50 patients, 80% (40/50) had fever of more than 1 month duration, of
which definitive diagnosis could not be made in 3 cases and were diagnosed as fever
of unknown origin.
Table No. 10 : Distribution of various opportunistic infections and other
manifestations.
Para met er
T u b ercu l osi s
Pe rc en tage of cases
68
P ul m onar y
20
Ex t ra -pul m onary
38
Bot h
10
Secondary bacterial infections
6
Neu rol ogi cal sy mp t oms
28
Tubercul a r m eni n gi t i s
50
Tubercul om a
14.28
TB a rachnoi di t i s
14.28
A IDS dem ent i a
7.14
P rogr essi ve m ul t i focal
l eucenc ephal o pat h y
Sexually transmitted diseases
14.28
4
Gonorrhoe a
2
Hepat i t i s B
2
Ren al Man i f estati on s
4
H IV associ at ed n ephropat h y
2
C hroni c renal f ai l ure
2
Fev er of u n k n ow n ori gi n
6
Mal i gn an cy
4
Non Hodgki ns l ym phom a
? Kaposi ’s S arco m a
2
2
2
Pe rsi sten t g en eral i zed
l ymp h ad en op ath y
6. DISCUSSION
The observations made in 50 cases of HIV infected patients admitted to
Yenepoya Medical College Hospital, Mangalore between October 2005 to September
2007, is discussed and compared with other studies.
1. AGE AND SEX:
Ghate M.V et a1
71
in his study on changing trends in clinical
presentation of HIV infected persons in Pune found that 88.1% of the cases were in
the age group between 21 years and 40 years and it was the male population that was
more affected as compared to the females with male to female ratio of 2.22:1.
Study done by Kothari K et a1 41 in 2001 showed that 90% of the cases were in
the age group of 20 to 40 years and male population constituted 83.33% with male to
female ratio of 5 : 1. In a study done by Mandal A.K et a1 7 2 , 81.16% of cases were
in the age group of 20 to 40 years with male to female ratio of 1.5: 1.
The age of the patients in the present study ranged from 20 to 61 years with
90% males and 10% females with a male to female ratio of 9 :1.
The incidence of maximum number of HIV infected cases in the age group of
20 to 40 is comparable with other studies.
This finding of male preponderance is comparable with other studies that the
incidence of HIV infection is more common in males than females. This data suggests
that sexually active population is more affected.
The comparable studies are shown in a tabular column below.
Total
Study series
number of
patients
patients
Males
Females
21- 40
M:F
in %
in %
years in%
Mandal A.K 72 et al
88
60.87
39.13
1.5:1
81.16
30
83.33
16.66
5:1
90
2801
68.97
31.02
2.22 :1
88.1
50
90
10
9:1
70
(2000)
Kothari K 41 et al
(2001)
Ghate M.V 71 et al
(2002)
Present study
2. Occupation:
M a n d a l A . K 7 2 et al in his study found that the main risk groups were
truck drivers and labourers. Study done by Kothari K41 et al showed that major risk
group were people in transport services constituting 40% of all cases.
In the present study people in transport services constituted 34% of all cases
and Hotel workers constituted 22% of all cases.
This finding is comparable with other studies that the incidence of HIV
infection was high among people working in transport probably because of longer
duration of stay away from the family.
Occupation
Mandal AK
72
et
al (2000 in %)
Transport
11.36
Labourer
17.05
Kothari k
41 et
al (2001 in %)
40
20
Present Study
(%)
34
16
Farmers
-
16.67
10
Hotel worker
-
-
22
Female sex worker
10.22
-
-
Others
61.36
23.33
18
3. Mode of transmission:
John T.J 8 4 et al in his study showed that 90% of the patients had multiple sex
partners and heterosexual route was the major mode of transmission.
Rajasekaran S73 et al showed heterosexual promiscuty in 74.4% of patients.
Of the remaining, 15.38% were females who had acquired the infection
through their HIV infected husbands while remaining 10.25% constituted
commercial sex workers and intravenous drug abusers.
Kothari K41 et al in his study showed that heterosexuality accounted for 90% of
the total cases.
In this study, heterosexual mode of transmission was the major mode of
transmission in 64%; 10% showed homosexual and in the remaining 24% of the cases
reliable history could not be elicited.
This finding is not comparable with other studies.
4. Presenting symptoms
A study of common presenting symptoms and signs was made. We noted that
fever and weight loss were the most common presenting symptoms constituting 80%
and 84% of cases respectively. This finding is comparable with other studies done by
Colebunders R 7 4 et al, showed fever and weight loss in 21.83% and 29.31%,
Lakshmi V . 7 8 et al in 61% and 45%, Kothari K4 1 et al in 96% and 66% of cases.
Then next common symptom in our study was cough > 1 month in 58% of cases
which was comparable with study done by Kothari K 4 1 et al who showed cough > 1
month in 60% of cases. However in studies done by Colebunders
74
R et al and
Lakshmi V 7 8 et al, only 15.5% and 11% of cases had cough respectively.
We see that present study has reported a higher incidence of cough >1 month
as compared to the two above mentioned studies. This could be explained by higher
incidence of tuberculosis in the present study.
Next common symptom reported in the present study was diarrhea >1 month,
in 22% of cases. This finding is comparable with studies done by Lakshmi V78 et al
and Kothari K41 et al which showed an incidence of 23% in both the studies.
However in a study done by Colebunders R the above mentioned symptom
was seen in only 9.77% of cases, which is lower incidence compared to the present
study.
Pain abdomen was seen in 20% of cases in the present study. However
Lakshmi
V78
et al reported in 9% of cases and Kothari K 4 1 et al in 6.6% of cases.
This study showed a higher incidence of this symptom compared to the above
mentioned studies.
Altered sensorium was seen in 4% of cases in present study. Kothari K41 et al
reported the same in 26% of cases. The present study had recorded a lower incidence
as compared to the study done by Kothari K et al, probably due to the small study
group in our study when compared to the other.
Dysphagia was seen in 4% of cases in the present study.However Kothari K41
et al reported in 30% of cases.
The table showing the comparable studies is given below
Colebunder
R 74
et al (1987)
%
Lakshmi
Kothari Present
V78
K 41 et al Study
et al (1998)
(2001)
%
%
Fever > l m o n t h
21.83
61
96
80
Weight loss
>10%
29.31
45
66
84
Cough >Imon th
15.51
11
60
58
Diarrhea > I month
9.77
23
23
22
Pain abdomen
-
9
6.6
20
Altred sensoru m
-
-
26
4
Dysphagia
-
-
30
4
5. Clinical findings in general examination:
The present study showed that skin lesions were present in 12% of patients,
oral candidiasis in 26%, significant lymphadenopathy in 40% and genital ulcer in 2%
of cases. Much lower incidence were reported in studies by Colebunders R 7 4 et al,
who reported skin lesions in 4.02%, oral candidiasis in 9.77%, lymphadenopathy in
7.47% and genital ulcer in 2.87%.
Lakshmi V 7 8 et al reported oral candidiasis in
6%, lymphadenopathy in 6% and genital ulcer in 5% of cases. However Kothari K41
et al reported a much higher incidence of skin lesions in 33%, oral candidiasis in 70%,
lymphadenopathy in 43% and genital ulcers in 23% of patients.
The table showing comparable studies is given below.
Oral
Skin
Lymphadeno
Study Series
candidiasis
Lesions%
pathy %
%
Genital
Ulcer%
Colebunders
R74 et
al(1987)
4.02
9.77
7.47
2.87
Lakshmi V78
et al(1998)
-
6
6
5
Kothari K41
et al(2001)
33
70
43
23
Present
study
12
26
40
2
Opportunistic infections and other associated conditions
i n H I V infected cases:
a.
Tuberculosis:
In the present study most common opportunistic infection was tuberculosis
with an incidence of 68%. 38.23% had only pulmonary tuberculosis, 38.23% had only
extrapulmonary tuberculosis and 23.54% had both pulmonary and extra pulmonary
tuberculosis. However much higher incidence of pulmonary tuberculosis and lower
incidence of extra pulmonary tuberculosis was shown by other studies done by Hira
S.K76 et al who reported 65.34% pulmonary, 27.84% extra pulmonary and 6.82%
both pulmonary and extra pulmonary tuberculosis. RajasekaranS73et al showed
55.6% of pulmonary tuberculosis and 30.5% combined disease. Zuber Ahmed77et al
showed 74.7% pulmonary tuberculosis, 19.8% extra pulmonary tuberculosis and 5.5%
combined disease. However Chacko S
40
et al reported a lower incidence of
pulmonary tuberculosis of 30% and higher incidence of combined disease with 48%
and extra pulmonary tuberculosis constituting 22%, when compared to above
mentioned studies.
The comparable studies are given below :
Tuberculosis
Chacko
Hira
S4 0 et al
S.K7 6 et
(1995)
al(1998)
%
Pulmonary
Extra
pulmonary
Combined*
%
R a j a e karan
S 73 et al
(2000) %
Zuber
Ahmed77
Present
et al
Study
(2003) %
30
65.34
55.6
74.7
38.23
22
27.84
13.9
19.8
38.23
48
6.82
30.5
5.5
23.54
* Both pulmonary and extrapulmonary
Chest X-ray Findings and HIV infection :
In the present study, 28 patients showed radiological abnormalities with upper
zone lesions in 17.8%, B/L infiltrations in 46.42%, lower zone lesions in 10.71%,
pleural effusion in 10.71%, pneumothorax in 3.57%, miliary shadow in 7.14% and
cardiomegaly in 3.57%. These findings were comparable with other studies done by
Chacko S
40
et al who reported upper zone lesions in 26.92%, B/L infiltrations in
23.07%, lower zone lesions in 7.69%, pleural effusion in 15.38%, pneumothorax in
3.84%, military shadows in 3.84% and hilar adenopathy in 19.23%.
Arora
79
et al reported upper zone lesions in 17.65%, B/L infiltrations in
29.42%, lower zone lesions 11.75%, pleural effusion in 17.65%, military shadows in
5.89% and hilar adenopathy in 17.65%.
However Agarwal
75
et al reported a higher incidence of typical upper zone
lesions in 57.1%, B/L infiltrations in 28.5% and lower zone lesions in 14.3% of cases
Table showing comparable studies is given below
Aggarwal
S.K 75 et al
(1993) %
Chacko
S40 et al
(1995)
17.65
26.92
57.1
17.8
29.41
23.07
28.5
46.42
11.75
7.69
14.3
10.71
17.65
15.38
-
10.71
-
3.84
-
3.57
5.89
3.84
-
7.14
B/L hilar
B/L hilar
Radiological Arora
lesions
Upper zone
79
et al
(2003)
Present
Study
lesions
B/L
infiltrations
Lower zone
lesions
Pleural
effusion
Pneumothorax
Military
shadows
Cardiomegaly
-
Any other
adenopathy
adenopathy
17.65
19.23
3.57
Neurological manifestations in HIV disease:
In the present study, 28% of patients had neurological complications. Of
these 50% of patients had meningitis with all the cases being tubercular meningitis.
We did not have any patients with cryptococcal meningitis. However studies done by
Lakshmi
78
et al reported meningitis in 70.59% of cases with 76.16% of them being
tubercular, cryptococcal meningitis in 12.5% of cases and syphilitic meningitis in
8.33% of cases.
Sircar AR
81
et al reported meningitis in 58.33% of cases with tubercular
meningitis in 42.86% of cases and cryptococcal meningitis in 57.14%.
Wadia R.S 80 et al reported meningitis in only 17.88% of cases with majority of
them being cryptococcal in etiology constituting 67.44% of the total meningitis cases.
Tubercular meningitis was seen in 18.6%, aspectic meningitis in 4.65%, pyogenic
meningitis in 5.81%, syphilitic in 2.32% and both cryptococcal and tubercular
meningitis in 1.16%.
The above two mentioned studies reported much higher incidence of
cryptococcal meningitis when compared to the present study. This could be explained
by very large sample size in those studies.
The present study showed tuberculoma in 14.28% of cases, spinal cord
involvement in the form of myelo radiculopathy in 14.28%, AIDS dementia complex
in7.14% and progressive multifocal leuco encephalopathy in 14.28%.
However the other studies had not reported any cases of progressive multifocal
leuco encephalopathy or muscular dystrophies or myopathies.
Lakshmi78 et al had reported tuberculoma in 5.88% of cases, myelo
radiculopathy in 5.88% of cases and toxoplasma infection in 17.65% in contrast to the
present study where we did not find toxoplasma infection affecting central nervous
system in any case.
Sircar AR
81
et al reported AIDS Dementia complex in 16.67% of cases and
sensori motor neuropathy in 25% of cases.
Wadia RS
80
et al reported myelopathy in 4.36% of cases, ADC in 4.36%,
neuropathies in 28.27% of cases and cranial neuropathies, seizures-, headache strokes,
altered sensorium, meningism constituted 45.13% of cases.
However present study did not report any neuropathies in comparison to the
above two studies.
The table showing the comparable studies is given below:
Sircar
A R 8 1 et al
et al (1998)
(1998)
Lakshmi 78
Meningitis
a.
b.
c.
d.
e.
f.
Tubercular
Cryptococcal
Aseptic
Pyogenic
Syphi litic
Combined
Wadia
R.S 80 Present
et al Study
(2001)
17.88
50
70.59
58.33
79.16
12.5
8.33
-
42.86
57.14
-
18.6
67.44
4.65
5.81
2.32
1.16
100
-
Tuberculoma
5.88
-
-
14.28
Myelopathy/
Myeloradiculopathy
5.88
-
4.36
14.28
-
16.67
-
7.14
-
-
-
14.28
Toxoplasma17.65
Neuropathy
– 25%
AIDS Dementia
Complex
Myeloradiculopathy
Progressive Multifocal
Leucencephalopathy
Any other
Neuropathy–
29.27%
Others –
45.13
-
Sexually transmitted diseases (STD) and HIV
The present study reported one patient having Hepatitis B and one patient
with genital gonorrhoea constituting 2% each of total cases. This finding is
comparable with study done by
Lakshmi 78 et al which reported Hepatitis B in 2.3%
of cases and Syphilis in 0.5% of cases. However much higher incidence of STDs was
reported by Shah H82 et al who showed presence of syphilis in 10% of cases,
Chancroid in 10%, Herpes genitalis in 15%, Condyloma accuminata in 10%,
balonoposthitis in 30%, Candidialvaginitis in 15% and non specific urethritis in 10%
of cases.
Sayal SK
83
et al reported chancroid in 32.5%, syphilis in 23%, LGV in
11.9%, gonorrhoea in 2.6% and herpes genitalis in 3.2% cases.
This higher incidence of STD could be explained because their study was
conducted in patients attending STD clinics.
Secondary bacterial infections and HIV
In the present study, out of 50 cases, 2 cases had pneumonia caused by gram
negative bacilli and 1 patient had chronic suppurative otitis media.
However in a study done by Kothari K 41 et al reported secondary infections in
7 patients (7/30) out of which 3 had pneumonia, 2 had lung abscess, 1 case had
pyogenic meningitis and 1 had acute suppurative otitis media. Chacko S
40
et al
reported 18 cases of secondary infection with 11cases of pneumonia, 3 had urinary
tract infection, 2 had enteric fever, 1 borderline lepromatous leprosy and 1 had
gastroenteritis due to Shigella Sonnei.
The present study reported lesser incidence of secondary bacterial infections
when compared to the above mentioned studies.
Persistant Generalised Lymphadenopathy (PGL):
The present study reported PGL in 2% of cases which was much lower when
compared to studies done by Kothari K 41 et al who reported PGL in 20% of cases and
Sircar 81 et al in 22.5% of cases.
Renal involvement and HIV:
The present study reported 1 (2%) case of chronic renal failure and 1 (2%)
case of HIV associated nephropathy. This finding is comparable with the study done
by Kothari K4 1 et al who reported HIV associated nephropathy in 3.3% of cases and
renal involvement in the form of albuminuria and hematuria in 7% of cases.
Malignancies and HIV :
The present study reported 1 case of Non Hodgkin's lymphoma and 1 case of
suspected Kaposi's sarcoma which is comparable with other studies done by Kothari
K41 et al who reported 1 case of Non Hodgkins lymphoma.
Chacko S40 et al reported 1 case of Non Hodgkins lymphoma and 2 suspected
lymphomas where definitive diagnosis could not be done because of lack of facilities.
In many resource poor countries, clinicians are severely limited in the use of
standard of care assays to help determine disease progression in HIV positive
patients. This limitation can result in a potentially dangerous postponement of the
initiation of antiretroviral therapy.
110-116
Previous studies had shown that TLC is a
low cost and useful tool for monitoring HIV progression and triggering
Opportunistic infection prophylaxis in resource poor settings.
In these settings WHO recommends using the total lymphocyte count (TLC)
as a surrogate marker for the CD4 T cell count. If the CD4 lymphocyte count is not
available, WHO recommends initiating HAART in WHO stage II and III disease
when accompanied by a TLC of less than 1200 cells/cmm.
Depletion of CD4+ T cells is one of the hallmarks of progression of HIV-1
infection and CD4 count has been established to be a standard laboratory marker of
disease progression in HIV3, 114,. However in many resource limited countries, the
cost of CD4 count are so high relative to reduced prices of antiretroviral drugs, that
routine monitoring of therapy would often be more expensive than the supply
of drugs themselves. Also unavailability of sophisticated laboratory equipments to
measure CD4+ count preludes their use in large parts of the world. Previous studies
had suggested that the total lymphocyte count (TLC) can be used to predict a low
absolute CD4+ T cell.3,102-105,
According to WHO recommendation, when CD4 testing is unavailable, then
patient can be started on HAART therapy, if patient has
 WHO stage IV disease irrespective of total lymphocyte count.
 WHO stage II or III disease with total lymphocyte count 1200 cells/cmm.
Treatment is also recommended for patients with advanced WHO stage II
disease including recurrent or persistent oral thrush and recurrent invasive bacterial
infections irrespective of CD4 count or TLC.
We undertook to look at the correlation between the CD4 count and TLC in
HIV patients with advanced disease. CD4 counts of 200 or less were correlated
with total lymphocyte count of 1200 or less.
It was also noted that patients had a mean CD4 count of 175 cells/mm 3 and
patients
had a mean TLC of 1338 cells/mm3. These observations were comparable with
other study groups.
On calculating linear correlation between CD4 count of <200 cells/mm3 and
TLC of <1200 , there was high statistical significance with sensitivity of 91%,
specificity of 53% and positive predictive value of 70% .
The scatter diagram shows that as the CD4 count level increases the TLC
level also increases and there was a significant correlation between CD4 and TLC.
The values of our study were correlated with other national and international studies
Place
NO. of
pts
John
Hopkins
University
1451
Aim
Correlation
TLC & Hb% to
predict
CD4
<200
before
initiation
of
HAART
Sensitivity
78%
70.7%
YRG
centre
for
AIDS
research and
education
Chennai,
India
To evaluate the
correlation
of
TLC to CD4
count
73%
Specificity
YMCH,
Mangalore
50
To correlate
b/w CD4 count
& TLC
91%
TLC
<1200
cells/mm3
significantly
predict CD4
count <200
<1200
TLCC <1200
cells/mm3
significantly
predict CD4
count <200
81.8%
<1400
Correlated
with
CD4
<200 cell/mm3
TLC
<1700/
CD4<350
Significant
correlation
b/w
TLC<1700
and CD4 <350
cells/mm3
50%
86%
53%
Results
<1200
37.3%
650
70%
TLC for
CD4 <200
cells/mm3
TLC
of
Significant
1200
or correlation
less
b/w CD4 <200
correlate
& TLC 1200
with CD4
count 200
Apart from the studies mentioned above, R Wood, F Post and G Maartene,
(CapeTown, South Africa).117 also studied CD4 and total lymphocyte counts as
predictors of HIV disease progression and concluded that for each clinical stage, a
significant difference in progression to AIDS and mortality was predicted by TLC
above or below 1250 cells/mm3. Survival and progression to AIDS occurred at
similar rates in patients with TLC 1250 cells/mm3 or CD4 count of 200 cells/cmm.
Another study done by Beck EJ106 et al, at Academic Department of Public
Health, St Mary's Hospital Medical School, London, UK on 1534 paired Total
Lymphocyte count and CD4 count, a significant correlation did exist and the high
correlation between total and CD4 lymphocyte counts, especially for patients with
symptomatic HIV disease, demonstrated the suitability of the use of TLC in the
absence of CD4 counts. Given the considerably lower prices of TLCs
compared with T- cell subset analysis, this is particularly relevant for developing
countries106
To summarize, a total of 15,102 patients enrolled in 15 different studies was
followed up to determine the ability of the total lymphocyte count to predict the CD4
cell count and HIV disease stage.
108
Eleven of these studies (which induced a
total of 11,713 patients) contained data that, overall, indicated support for the
predictive ability of the total lymphocyte count, where as four had concluded
that TLC was not a reliable predictor of the CD4 cell count.108
Studies done in John Hopkins University Bloomberg School of Public Health
analyzed stated that a TLC decline of greater than 10% per year and Hemoglobin decline of
greater than 22% per year was noted in over 77% of study participants who developed
AIDS109-110
The pattern of CD4+ counts over time is more important than any single
CD4+ count value. CD4+ counts generally decrease as HIV progresses. Therefore it is
more valuable to evaluate a series of CD4+ counts than any single count.110
As the CD4 count is affected by the time of the day (lower in the
morning), in acute illness, refrigeration of blood sample (decrease CD4+ counts) or
with rough handling or contamination of blood sample , serial recording of
TLC and hemoglobin can give an equally stable reflection of progression of disease
and development of AIDS in HIV positive patients.108
It becomes more feasible specially in developing countries as a CD4 count costs
around $ 30 US while TLC costs around 0.80 US $, 107 monitoring the patient with
TLC will have an enormous cost benefit in patients with limited resources.
Limitations of this study necessitate further investigations. As this was an
observational study of subjects in Mangalore , more assessment of TLC using data
from the target countries are needed. Conditions specific to resource limited
settings, such as the higher prevalence of leucocytosis due to inter current
infections, may influence the interpretability of changes in TLC. Further, as has been
shown with CD4 count, TLC values as well as the dynamics of the measure may vary
across different ethnicities. Region-specific validation of CD4 and TLC changes on
HAART are needed. Also, TLC measured by complete blood count may not be
possible in very low income countries or remote regions. Therefore, the evaluation
of TLC measured by light microscopy and manual cell counting may be beneficial.
7. CONCLUSION
 In this study we conclude that most of the clinical observations were in
accordance with the other studies conducted earlier. The study showed male
preponderance with heterosexual mode of transmission being the commonest
mode of transmission. Fever, weight loss and diarrhea continue to be the
presenting symptoms. Tuberculosis was the most common opportunistic
infection. Among various neurological manifestations, tubercular meningitis
was the commonest and unlike in other studies, there was absence of
cyptococcal meningitis and toxoplasmosis in our study.
 Thus HIV infection can present with varied manifestations depending on
geographic, socio-economic and cultural environment and thus needs a high
index of suspicion for early detection of case and management.

Our study shows a definite correlation between TLC and CD4 count in HIV
positive patients. CD4 counts of less than 200 cells/mm3 showed a satistically
significant correlation with TLC of less than 1200 cells/mm3

TLC can be substituted for the CD4 count when the latter is unavailable and
HIV related symptoms exist.
 TLC could be used as a low cost tool and as a surrogate marker for monitoring
HIV disease and its progression.

These results could be very useful for regions with scarce health care
resources as an alternative way of identifying individuals who should receive
HAART therapy for HIV infection. We believe further research in appropriate
population is warranted.
 For the people who may not be able to afford the treatment and may get free
supply of antiretroviral medicine, TLC can serve as a cost effective, affordable
index to start HAART treatment and also to monitor HAART treatment
8. SUMMARY
A prospective study of 50 cases of HIV infected cases was done,
diagnosed on the basis of a positive rapid spot test and confirmed by positive ELISA,
admitted to Yenepoya Medical College Hospital between october 2005 to september
2007. Available literature on HIV infection was scrutinized.

The study showed a male to female ratio of 9:1 and the maximum incidence
was seen between 20 to 40 years.

The study showed more incidence of HIV infection among people working in
transport as drivers, with heterosexual mode of transmission as the most
common mode of transmission.

Most common presenting symptoms were weight loss and fever >1 month.
Among the other associated symptoms cough > 1 month was seen in 58%,
diarrhea > 1 month in 22%, pain abdomen in 20%, altered sensorium and
dysphagia in 4% each.

Skin lesions were seen in 12% of the cases, oral candidiasis in 26%,
lymphadenopathy in 40% and genital ulcer in 2%.

Tuberculosis was the most common opportunistic infection seen in this study,
that is in 68% of cases.

Neurological complications were seen in 28% of patients, most common being
tubercular meningitis in 50% of cases.

Other sexually transmitted diseases were seen in only 2 patients, 1 had
hepatitis B and the other had genital gonorrhoea.

Persistant generalized lymphadenopathy was seen in 1 case.

In this study, 1 case had HIV associated nephropathy and 1 case had chronic
renal failure.

Out of 50 cases, 1 case had Non Hodgkin's lymphoma and 1 case had
suspected Kaposi's Sarcoma, which needed further study by
immune histo
chemistry.

This study showed a definite correlation between TLC and CD4 count in HIV
positive patients. Based on this study TLC of 1200cells/mm3 may be
substituted for CD4 count of 200 cells/cmm, when CD4 count is unavailable
and HIV related symptoms exist.
Thought for the future
On the eve of World AIDS Day in December 2003, as WHO released its 3 by
5 programme, the Government of India announced a commitment to begin providing
antiretroviral treatment free of charge to selected group of patients in April 2004 and
to place 1 lakh people on HAART treatment within a year. WHO HIV/AIDS
specialists are being deployed to each of the six high burden states, with other
initiatives aimed at supporting the country on issues such as clinical management,
drug procurement, laboratory support and routine monitoring and evaluation.
Therefore in resource limited settings, like our country, total lymphocyte count
can be used as a surrogate for initiating and monitoring HAART therapy.
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